Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA‐B27 transgenic rats

SUMMARY Germ‐free HLA‐B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen‐free (SPF) bacteria induces colitis accompanied by immune activation. To study host‐dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA‐B27 TG versus nontransgenic (non‐TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL‐stimulated unseparated T‐ or B‐ cell‐depleted MLN cells from HLA‐B27 TG and non‐TG littermates were analysed for IFN‐γ, IL‐12, TNF, IL‐10 and TGF‐β production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN‐γ, IL‐12 and TNF than did non‐TG MLN cells. In contrast, CBL‐stimulated non‐TG MLN cells produced more IL‐10 and TGF‐β. T cell depletion abolished IFN‐γ and decreased IL‐12 production, but did not affect IL‐10 and TGF‐β production. Conversely, neither IL‐10 nor TGF‐β was produced in cultures of B cell‐depleted MLN. In addition, CD4+ T cells enriched from MLN of HLA‐B27 TG but not from non‐TG rats produced IFN‐γ when cocultured with CBL‐pulsed antigen presenting cells from non‐TG rats. Interestingly, IL‐10 and TGF‐β, but not IFN‐γ, IL‐12 and TNF were produced by MLN cells from germ‐free TG rats. These results indicate that the colitis that develops in SPF HLA‐B27 TG rats is accompanied by activation of IFN‐γ‐producing CD4+ T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation.